RGD Reference Report - Interactions of epinephrine, norepinephrine, dopamine and their corresponding alpha-methyl-substituted derivatives with alpha and beta adrenoceptors in the pithed rat. - Rat Genome Database

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Interactions of epinephrine, norepinephrine, dopamine and their corresponding alpha-methyl-substituted derivatives with alpha and beta adrenoceptors in the pithed rat.

Authors: Ruffolo RR, JR  Goldberg, MR  Morgan, EL 
Citation: Ruffolo RR Jr, etal., J Pharmacol Exp Ther. 1984 Sep;230(3):595-600.
RGD ID: 2301946
Pubmed: PMID:6381693   (View Abstract at PubMed)

The effects of alpha-methyl substitution of epinephrine, norepinephrine and dopamine were investigated at alpha-1, alpha-2, beta-1 and beta-2 adrenoceptors in the pithed rat. alpha-Methyl substitution of these three phenethylamines variably altered their capacity to elicit alpha adrenoceptor-mediated vasoconstriction, with slightly enhanced potency being observed for alpha-methyl substitution of norepinephrine and dopamine and a marked reduction in potency for alpha-methyl substitution of epinephrine. However, in all instances, alpha-methyl substitution resulted in a higher selectivity for alpha-2 adrenoceptors (over alpha-1 adrenoceptors). Thus, while epinephrine, norepinephrine and dopamine all produced vasoconstriction that was mediated equally by postsynaptic vascular alpha-1 and alpha-2 adrenoceptors, their corresponding alpha-methyl-substituted derivatives produced vasoconstriction exclusively by activation of postsynaptic vascular alpha-2 adrenoceptors. The beta-1 adrenoceptor-mediated chronotropic effects of these phenethylamines were inconsistently affected by alpha-methyl substitution, with an increase in potency being observed for alpha-methyl substitution of norepinephrine and decreases in potency being observed for alpha-methyl substitution of epinephrine and dopamine. In marked contrast, alpha-methyl substitution of epinephrine, norepinephrine and dopamine was associated with consistent and dramatic increases in potency for beta-2 adrenoceptor-mediated vasodepressor activity. These results indicate that alpha-2 and beta-2 adrenoceptors possess the unique ability to recognize and/or accept alpha-methyl substituents on phenethylamines and that this ability is not shared by their respective receptor subtypes, the alpha-1 and beta-1 adrenoceptors. Furthermore, the results show that alpha-methylepinephrine is a potent beta adrenoceptor agonist, with an apparent 500-fold selectivity for beta-2 adrenoceptors over beta-1 adrenoceptors.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to catecholamine involved_inIDA 2301946 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adrb2  (adrenoceptor beta 2)

Objects referenced in this article
Gene Adrb1 adrenoceptor beta 1 Rattus norvegicus

Additional Information